DESCRIPTION (Adapted from the applicant's description) Despite decades of focused investigation, the function of sleep is not known. The best-supported hypothesis is that sleep promotes optimal neural plasticity. Given that neural plasticity is a necessity for invertebrates as well as higher vertebrates, these investigators propose that a likely function of a sleeplike rest state in Drosophila melanogaster, is also to promote optimal neural plasticity. As in mammals, neural plasticity Drosophila accompanies the consolidation of long-term memory, the molecular basis of which is rapidly being characterized. A sleeplike rest state, with a robust rebound after deprivation, has been identified in preliminary studies of Drosophila. Therefore, the proposed studies will focus: (1) on determining the behavioral and molecular properties of the sleeplike rest; and (2) on testing the hypothesis that this state is a functional analog of mammalian sleep in that it promotes neural plasticity. The association between sleeplike rest and learning will be studies by dissecting the molecular link between rest and expression of cyclic-AMP responsive genes. cAMP-responsive genes and the binding proteins that regulate them (CREBs) play a critical role in long-term memory consolidation in both vertebrates and invertebrates, including Drosophila. These preliminary studies show that CREB activity is highest during the night, when the rest period occurs. The hypothesis that rest promotes LTM in Drosophila will be tested directly by manipulating the rest period and assaying long term memory consolidation behaviorally. The proposed studies bring to bear the molecular tools that can readily be exploited in Drosphila because of its long history as a research subject in genetic and neurobiological studies. The overall hypothesis is that the function of the sleeplike rest phase in Drosophila is the facilitation of adaptive neural plasticity, specifically the consolidation of Long Term Memory. In Specific Aim 1 they will document that sleeplike rest in Drosophila is a defined behavioral syndrome. The focus will be on features that show analogy to mammalian sleep and on developing automated measures of sleeplike rest for use as tools in the subsequent studies. Specific Aim 2 will extend their preliminary findings that CREB activity increases in the dark phase, and test the hypothesis that its activity is linked to rest by specific molecular mechanisms. Finally, in Specific Aim 3, they will test directly the prediction that optimal long-term memory consolidation (LTM) requires a well-consolidated sleeplike rest states.